Georgia State Researchers Use ORNL Supercomputer to Gain New Insights Into DNA Repair

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Source: Chunli Yan, Georgia State University,
Source: Chunli Yan, Georgia State University,

August 6, 2023 | Originally published by Oak Ridge National Lab on July 7, 2023

Transcription factor IIH, or TFIIH, pronounced “TF two H,” is a veritable workhorse among the protein complexes that control human cell activity. It plays critical roles both in transcription — the highly regulated enzymatic synthesis of RNA from a DNA template — and in the repair of damaged DNA. But how can one protein assembly participate in two such vastly different and extremely important genomic tasks?

A team of researchers led by chemistry professor Ivaylo Ivanov of Georgia State University used the Summit supercomputer at the Department of Energy’s Oak Ridge National Laboratory to help answer that question. By conducting multiple molecular dynamics simulations of TFIIH in transcription and DNA repair-competent states and then contrasting the structural mechanisms at work, Ivanov and his team made an interesting discovery:  TFIIH is a shapeshifter, reconfiguring itself to meet the demands of each task.

Unraveling the inner workings of TFIIH at the interface of transcription and DNA repair is key for understanding the origins of genetic disorders caused by mutations — hereditary diseases such as xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. The GSU team published its results in the journal Nature Communications.

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